The controlled expression of genetic information in cells in culture and in transgenic animals is an essential tool in the study of gene function in vitro, and eventually will prove central to the treatment of disease by introduced genetic material (gene therapy). We showed previously that conditional expression of the v-ras-H oncogene from the glucocorticoid-responsive mouse mammary tumor virus (MMTV) promoter could result in a regulated cell phenotype, and demonstrated that regulated "phenotype switching" can be employed to study the oncogenic process in whole animals. The oncogenic potential of NIH 3T3 fibroblasts carrying the hormone- inducible v-ras-H oncogene was markedly enhanced when p21 expression was induced prior to inoculation of cells into the animal. These experiments underscored the potential applications of this technology in studying various processes in the intact animal. We are now developing a series of retrovirus-based vectors utilizing these principles that will permit us to explore the application of this approach to gene therapy in the human.